This study systematically evaluates the efficacy and safety of tirzepatide, a dual agonist of glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, in treating obesity. A total of 12 randomized controlled trials (RCTs) involving 11,758 patients were included. The results show that tirzepatide significantly reduces BMI, waist circumference, and body weight compared to GLP-1 receptor agonists (GLP-1 RAs), placebo, and insulin. Specifically, tirzepatide reduced BMI by -1.71, -3.99, and -4.02, waist circumference by -4.08, -7.71, and -9.15, and body weight by -5.65, -10.06, and -10.63, respectively. In terms of weight loss, tirzepatide showed a significant advantage in achieving a weight loss of ≥20% and ≥25% compared to placebo, with risk ratios of 30.43 and 37.25, respectively. The dose-dependent therapeutic effect was observed in subgroup analyses. Regarding safety, tirzepatide had a higher incidence of gastrointestinal adverse reactions compared to GLP-1 RAs but lower hypoglycemic risk compared to insulin. The incidence of other adverse events, including pancreatitis, cholecystitis, major adverse cardiovascular events (MACE-4), hypersensitivity reactions, and neoplasms, did not show significant differences compared to the control groups. Overall, tirzepatide demonstrated significant efficacy and good safety profile in treating obesity. The study concludes that tirzepatide is a promising treatment for obesity, with a strong potential to become a new weight loss drug. However, further research is needed to confirm its long-term safety and effectiveness.This study systematically evaluates the efficacy and safety of tirzepatide, a dual agonist of glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, in treating obesity. A total of 12 randomized controlled trials (RCTs) involving 11,758 patients were included. The results show that tirzepatide significantly reduces BMI, waist circumference, and body weight compared to GLP-1 receptor agonists (GLP-1 RAs), placebo, and insulin. Specifically, tirzepatide reduced BMI by -1.71, -3.99, and -4.02, waist circumference by -4.08, -7.71, and -9.15, and body weight by -5.65, -10.06, and -10.63, respectively. In terms of weight loss, tirzepatide showed a significant advantage in achieving a weight loss of ≥20% and ≥25% compared to placebo, with risk ratios of 30.43 and 37.25, respectively. The dose-dependent therapeutic effect was observed in subgroup analyses. Regarding safety, tirzepatide had a higher incidence of gastrointestinal adverse reactions compared to GLP-1 RAs but lower hypoglycemic risk compared to insulin. The incidence of other adverse events, including pancreatitis, cholecystitis, major adverse cardiovascular events (MACE-4), hypersensitivity reactions, and neoplasms, did not show significant differences compared to the control groups. Overall, tirzepatide demonstrated significant efficacy and good safety profile in treating obesity. The study concludes that tirzepatide is a promising treatment for obesity, with a strong potential to become a new weight loss drug. However, further research is needed to confirm its long-term safety and effectiveness.